The applicants are a group of 22 clinical units (45 hospitals), 5 core laboratories, and a data coordinating center, most of whom participated in the TIMI I and TIMI II studies, whose long-term objective is to resolve the major controversial issues currently complicating the management of patients with unstable angina and non-Q-wave MI. The proposed study, entitled "Thrompolysis in Myocardial Ischemia" (TIMI III), will utilize the expertise gained in the applicants' prior work with t-PA and PTCA for Q-wave MI, to determine the value of these new approaches for the related conditions of unstable angina and non-Q-wave MI--disorders which afflict approximately one million individuals annually in the United States. The group will conduct 2 randomized, blinded studies (TIMI IIIA and IIIB) directed toward two specific aims: (1) To determine if t-PA produces improvement in angiographically determined myocardial perfusion or coronary stenosis (TIMI IIIA); and, (2) to identify the optimal initial and follow-up management strategy (TIMI IIIB). Initially, is heparin, t-PA and/or t-PA plus heparin superior to the addition of placebo to conventional therapy? In follow-up, is there a need for routine angiography followed, if the anatomy is suitable, by revascularization? TIMI IIIA will be conducted by a group of 13 clinical units which will randomize 300 patients over a 9-month period. The effect of t-PA on angiographically determined coronary artery blood flow and stenosis will be determined by a Core Laboratory of Quantitative Angiography. TIMI IIIB will be conducted by 21 clinical units, which will randomize 2,000 patients over a 2-year period. Success of therapy will be judged by the number of patients who do not experience death, MI, disabling stroke, or failure of therapy (defined as significant recurrent ischemic pain at rest, or unsatisfactory results of Holter monitoring or an ETT with thallium). Core Laboratories for ECG/ETT analysis, qualitative angiography, ambulatory ECG, and radionuclide (thallium) studies will assure quality of data collection and provide centralized, blinded analysis of crucial endpoint data. The sample will be of sufficient size to establish clearly the risks versus benefits of heparin therapy, t-PA therapy and t-PA plus heparin therapy, as well as the value of routine angiography followed by revascularization, for these serious and frequent disorders.